Post-Prostatectomy Adjuvant Radiotherapy May Best Early Salvage Therapy

NEW YORK (Reuters Health) - Following prostatectomy, patients with prostate cancer who have adverse pathological features may benefit most from adjuvant radiotherapy, according to a multicenter cohort study.

As Dr. Jason A. Efstathiou told Reuters Health by email, "When surgery has probably failed to cure a patient, the best prospective data support the use of postoperative radiation therapy. The debate now centers on the optimal timing of such post-prostatectomy radiation therapy: Is it adjuvant (ART) for all (with adverse pathologic features) or early salvage (ESRT) for some (who experience biochemical failure)?"

In a January 25 online article in JAMA Oncology, Dr. Efstathiou of Harvard Medical School, Boston, and colleagues report on 1,566 patients who had undergone ART or ESRT from 1987 through 2013.

In all, 1,195 patients with prostate-specific antigen (PSA) levels <0.1 ng/mL received ESRT and 371 with PSA levels of 0.1 to 0.5 ng/mL received ART.

The 12-year actuarial rate of freedom from biochemical failure was 69% with ART and 43% with ESRT. Corresponding rates for freedom from distant metastases were 95% and 85%, respectively - and for overall survival, 91% and 79%.

Multivariable analysis for biochemical failure showed that, in addition to ART, lower Gleason score and T stage - and nodal irradiation - were among the favorable prognostic features.

To account for the unknown subset of patients in the ART group who would not have developed recurrence after surgery, the team performed a sensitivity analysis. It showed that the lower risk of biochemical failure associated with ART did not lose statistical significance until more than 56% of these patients were assumed to have been cured by surgery alone.

This threshold, the researchers note, "is greater than the estimated 12-year freedom from biochemical failure rate of 33% to 52% after radical prostatectomy alone."

Despite these encouraging findings, Dr. Efstathiou observed, "national practice patterns show us that the use of ART remains low (estimated at less than 10% of patients who meet the criteria of having adverse pathologic features). Our multi-institutional data suggest some benefit to ART (over ESRT), though these findings require validation in ongoing prospective studies."

"If indeed validated," he added, "contemporary practice patterns would need to be revisited. Emerging genomic biomarkers and advanced imaging may help with risk stratification and patient/treatment selection for ART and ESRT. Ultimately, the onus is on the uro-oncology team (urologist, radiation oncologist, medical oncologist) to discuss postoperative radiation therapy with the patient, address optimal timing when it is used based on the best available data, and provide justification when it is not."

Dr. Brian C. Baumann of Washington University School of Medicine, St. Louis, Missouri, told Reuters Health by email that the study "is a valuable contribution to the literature. It provides some of the best evidence to date in support of upfront radiation therapy after radical prostatectomy in select patients with adverse pathologic features rather than delaying radiation until men develop PSA recurrence."

Dr. Baumann, an assistant professor of radiation oncology, added, "Men who received upfront radiation therapy had lower rates of PSA recurrence, lower rates of distant metastases, and improved overall survival in this multi-institutional, retrospective study. The results warrant validation in prospective clinical trials, and several such trials may help to answer the question definitively, including the RADICALS trial, the GETUG-17 trial, and the RAVES trial."


JAMA Oncol 2018.



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